Over the past decade, there has been considerable interest in developing agents which are serotonin (5HT) antagonists, including compounds which block 5HT.sub.2 receptors. Such agents are useful in treating disease states in which an excess of serotonin is a major contributing cause. These disease states include hypertension, anorexia nervosa, depression, mania, carcinoid syndrome, migraine and vasospasm. Certain ergoline derivatives have been found to possess such activity; see, e.g., U.S. Pat. No. 3,580,916.
More recently, certain ergoline-8-carboxamides were found to be potent 5HT.sub.2 receptor blockers. EPO Patent Application Publication 296,748 reports the biological activities for a number of such derivatives, including a cyclopentyl amide of Example 9 and a 2-hydroxycyclohexyl amide (of undefined stereochemistry) in Example 14.
The present invention is directed to the discovery that certain stereochemically pure 2-hydroxycyclopentyl amides of ergolines are potent 5HT receptor blockers superior to these art compounds in suppressing serotonin-induced increases in mean arterial pressure in vivo.